Beta-amyloid and Memory
A hallmark of Alzheimerâ€™s disease pathology is the presence of beta-amyloid plaques in the brains of patients.
Thinking and Remembering Research into thinking and remembering brought mixed results in 2006: remarkable discoveries in some areas and exposure of the need to pause and reassess approaches in others. Alzheimerâ€™s Disease A hallmark of Alzheimerâ€™s disease pathology is the presence of beta-amyloid plaques in the brains of patients. Over the past decade or so, scientists have focused much of their work on these physical manifestations of the disease with the idea that if they could prevent the plaques from forming or remove them, they could mitigate the behavioral impact of the disease. However, several groups reported data in 2006 suggesting that these plaques themselves may not be the underlying cause of the disease. The beta-amyloid plaques are aggregates of a small peptide that is clipped off a larger protein called the amyloid precursor protein and released into the space between neurons. Previous work with mice that express human amyloid precursor protein demonstrated that behavioral abnormalities, such as deficits in spatial memory, are apparent well before the plaques appear. Thus either the protein fragments are not the problem or smaller aggregations, which do not look like plaques, are damaging the neurons. Hundreds or thousands of protein fragments make up a single plaque, but Sylvain LesnÃ© at the University of Minnesota Medical School in Minneapolis and colleagues found that small aggregates of just 12 fragments appeared at the same time as the animalsâ€™ memory started to fail. Moreover, when the researchers purified these small clumps from the brains of diseased animals and injected them into the brains of healthy animals, the healthy animals lost their ability to learn the physical layout of a maze. The research was reported in Nature.1 Similarly, researchers at the Buck Institute for Age Research in Novato, California, reported in Proceedings of the National Academy of Sciences that if the engineered mice expressed a protein variant from which beta-amyloid cannot be released, the mice lacked the plaques typical of Alzheimerâ€™s but still developed memory problems.2 Page: 1 2 3 4 References Thinking and Remembering 1. LesnÃ© S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, Gallagher M, and Ashe KH. A specific amyloid-beta protein assembly in the brain impairs memory. Nature 2006 440(7082):352â€“357. 2. Galvan V, Gorostiza OF, Banwait S, Ataie M, Logvinova AV, Sitaraman S, Carlson E, Sagi SA, Chevallier N, Jin K, Greenberg DA, and Bredesen DE. Reversal of Alzheimerâ€™s-like pathology and behavior in human APP transgenic mice by mutation of Asp664. Proceedings of the National Academy of Sciences USA 2006 103(18):7130â€“7135. 3. Bennett DA, Schneider JA, Arvanitakis Z, Kelly JF, Aggarwal NT, Shah RC, and Wilson RS. Neuropathology of older persons without cognitive impairment from two community-based studies. Neurology 2006 66(12):1837â€“1844. 4. Tabert MH, Manly JJ, Liu X, Pelton GH, Rosenblum S, Jacobs M, Zamora D,Goodkind M, Bell K, Stern Y, and Devan DP. Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. Archives of General Psychiatry 2006 63(8):916â€“924. 5. Apostolova LG, Dutton RA, Dinov ID, Hayashi KM, Toga AW, Cummings JL, and Thompson PM. Conversion of mild cognitive impairment to Alzheimer disease predicted by hippocampal atrophy maps. Archives of Neurology 2006 63(5):693â€“699. 6. Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S, Cannon A, Dwosh E, Neary D, Melquist S, Richardson A, Dickson D, Berger Z, Eriksen J, Robinson T, Zehr C, Dickey CA, Crook R, McGowan E, Mann D, Boeve B, Feldman H, and Hutton M. Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 2006 442(7105):916â€“919. . Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ, van Duijn C, Peeters K, Sciot R, Santens P, De Pooter T, Mattheijssens M, Van den Broeck M, Cuijt I, Vennekens K, De Deyn PP, Kumar-Singh S, and Van Broeckhoven C. Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 2006 442(7105):920â€“924. 8. Whitlock JR, Heyman AJ, Shuler MG, and Bear MF. Learning induces long-term potentiation in the hippocampus. Science 2006 313(5790): 1093â€“1097. 9. Gruart A, Munoz MD, and Delgado-Garcia JM. Involvement of the CA3-CA1 synapse in the acquisition of associative learning in behaving mice. Journal of Neuroscience 2006 26(4):1077â€“1087. 10. Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC. Storage of spatial information by the maintenance mechanism of LTP. Science 2006 313(5790):1141â€“1144.
beta, amyloid, precursor, protein, memory, Alzheimer, aging, age, pathology
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An overview of Alzheimer's disease-related content on Genes to Cognition Online.
Alzheimer's disease is characterized by abnormal plaques and tangles in the brains of patients.
Amyloid precursor protein (APP) is expressed in the synapses of neurons and is thought to be responsible for forming and repairing synapses.
Professor Donna Wilcock describes amyloid plaques as clumps of protein in the brain that are one of the three hallmarks of Alzheimer's disease.
Alzheimer’s disease is a progressive brain disorder that causes a gradual and irreversible loss of higher brain functions, including memory, language skills, and perception of time and space,
Professor Kenneth Kosik describes senile plaques, an extracellular collection of a-beta protein. It is one of the hallmarks of Alzheimer's disease.
PBS's 'Secret Life of the Brain' reviews research on the prevention and treatment of Alzheimer's disease.
Professor Dennis Selkoe discusses the age at which plaque-forming a-beta can begin to build up. Children with Down syndrome may have these plaques, otherwise childhood instances are rare.
Genes that can cause neurofibrillary tangles and amyloid plaques are strongly associated with Alzheimer's disease.
Professor Donna Wilcock discusses early-onset Alzheimer's disease, which can reach an advanced stage by the age of 50 or 60 years.